2012, Fellow of the American Association for the Advancement of Science2014, Indiana University Outstanding Faculty Collaborative Research Award2014, Fulbright US Research Scholar Award2015, American Society for Microbiology Divisional Lecturer

Research Description

Our research interests and experimental approaches range widely. We work to answer questions about bacterial development and life history, including the mechanisms that underlie observed phenotypes, and the evolutionary forces that shape them:

How do bacteria regulate the complex task of differentiation to create distinct cell types and morphologies?

How do individual bacteria coordinate their adhesion to surfaces? What role does adhesion play in community ecology?

Why do bacteria age, and what mechanisms drive the aging process?

As a model, we study the simple differentiating bacterium Caulobacter crescentus in which each cell division produces a motile swarmer cell and a stalked cell. In addition to differences in morphology, the two progeny cells have different fates. Only the stalked cell is competent to replicate DNA and divide. We increasingly study non-model bacterial species related to Caulobacter in order to bring an evolutionary perspective to our studies.

Caulobacter is easy to grow, has excellent genetics and a sequenced genome, and is ideally suited for cell biological approaches. We use a multitude of approaches that include mathematical modeling, biophysics, biochemistry, molecular biology, cell biology, microscopy, genetics, genomics, and proteomics. Our wide range of expertise and excellent collaborators allow us to focus on biological questions rather than specific methods and provides an outstanding multidisciplinary environment.

Regulation of cell differentiation. The different stages of polar development in Caulobacter are tightly coordinated with the cell cycle. We study transcriptional and proteolytic regulatory mechanisms and regulators that control the timed and ordered progression of these stages. We also study a checkpoint that couples polar development with cell division.

Control of cellular asymmetry. Before they divide, Caulobacter cells are asymmetric with a flagellum at one pole and a stalk and adhesive holdfast at the other pole. We have used genetic and molecular methods to identify genes that are involved in the maintenance of cellular asymmetry and we are studying their mechanism of action. We also have a strong interest in the mechanisms that target proteins and structures to a specific pole of the cell

Bacterial adhesion and biofilm formation. Adhesion is an important component of bacterial infections and is the first step of biofilm formation. In Caulobacter, adhesion is mediated by the holdfast, a complex polysaccharide with strong adhesive properties found at the tip of the stalk. We study the mechanism and regulation of single cell attachment to surfaces, holdfast synthesis, and the subsequent events that lead to the formation of biofilms.

Evolutionary genomics. We are taking advantage of next generation sequencing methods to sequence the genome of bacteria closely related to Caulobacter to investigate the evolution of cell shape and differentiation and the regulatory networks that control them. Towards this goal, we are isolating bacteria related to Caulobacter from a variety of environments using a phylogeny based screen to avoid the bias due to isolations based on phenotype.

Bacterial aging. Recent work has shown that organisms previously thought to be immortal, such as bacteria, demonstrate age-specific declines in reproduction. Asymmetry is thought to be important for aging by allowing the preferential segregation of damaged molecules to mother cells. We are using the asymmetrically dividing Caulobacter and close relatives that divide by the even more asymmetric mechanism of budding such as Hyphomonas to address the mechanism of aging and the role of asymmetry in this process.